Stable tracer investigations in humans for assessing the biokinetics of ruthenium and zirconium radionuclides.

The interest in the biokinetics of ruthenium and zirconium in humans is justified by the potential radiological risk represented by their radionuclides. Only a few data related to the biokinetics of ruthenium and zirconium in humans are available and, accordingly, the biokinetic models currently recommended by the ICRP for these elements are mainly based on data from animal experiments. The use of stable isotopes as tracers, coupled with a proper analytical technique (nuclear activation analysis with protons) for their determination in biological samples, represents an ethically acceptable methodology for biokinetic investigations, being free from any radiation risk for the volunteer subjects. In this work, the results obtained in eight biokinetic investigations for ruthenium, conducted on a total of three healthy volunteers, and six for zirconium, performed on a total of three subjects, are presented and compared to the predictions of the ICRP models.

Synthesis and X-ray characterization of the phosphido-carbonyl cluster anions.

The [Co(9)P(CO)(21)](2)(-) anion has been isolated from the products of the reaction between Na[Co(CO)(4)] and PCl(5) in tetrahydrofuran at reflux. The structure of the cluster anion [Co(9)P(CO)(21)](2)(-) in its tetraphenylphosphonium salt has been elucidated by X-ray analysis. The crystals are monoclinic, space group P2(1)/n, a = 12.528(3), b = 14.711(5), c = 19.312(6) A, beta = 93.68(2) degrees, Z = 2. Final R = 0.065 for 2300 unique reflections having I > 3sigma(I). The anion, which is disordered about an inversion center, consists of a monocapped square antiprismatic cluster containing an interstitial phosphide and surrounded by 13 terminal and 8 edge-bridging carbonyl ligands. Average values are: Co-Co 2.685 A, and Co-P 2.256 A. The [Co(10)P(CO)(22)](3)(-) anion has been obtained by condensation of the [Co(9)P(CO)(21)](2)(-) anion with [Co(CO)(4)](-) in tetrahydrofuran at reflux. While the [Co(9)P(CO)(21)](2)(-) anion is stable under CO, the [Co(10)P(CO)(22)](3)(-) anion is decomposed to [Co(9)P(CO)(21)](2)(-) and [Co(CO)(4)](-). The benzyltrimethylammonium salt of the [Co(10)P(CO)(22)](3)(-) anion has been studied by X-ray analysis. It gives triclinic crystals, space group P_1, a = 11.452(3), b = 23.510(6), c = 25.606(4) A, alpha = 112.46(1), beta = 95.79(1), gamma = 73.548(2) degrees, Z = 4. Final R = 0.041 for 8600 unique reflections having I > 3sigma(I). There are two independent trianions in the asymmetric unit, both showing similar geometries, consisting of bicapped square antiprismatic clusters with a central P atom, each bearing 10 terminal and 12 edge-bridging carbonyl ligands, 8 of which, bound to the capping metals, are markedly asymmetric. Average values are: Co-Co 2.678 A, and Co-P 2.262 A. Electrochemistry shows that [Co(9)P(CO)(21)](2)(-) and [Co(10)P(CO)(22)](3)(-) in acetonitrile solution undergo either a one-electron oxidation or a two-electron reduction. This latter process appears as a single step in the case of the dianion and as two separated one-electron steps in the case of the trianion. All the processes are accompanied by slow chemical complications, thus testifying that no stable redox congeners exist for these phosphide clusters.

Determination of biokinetic parameters for ingestion of radionuclides of zirconium in animals using stable tracers.

Exposure to the radioactive isotope 95Zr, as in nuclear accidents, and to stable zirconium, due to its use in industry, has increased the interest in the biokinetics of this element. Information has been derived mainly from tests performed on animals by means of radioactive tracers. Due to the fact that extrapolation from animals to humans is always open to question, there is an increasing need of a methodology which allows data to be obtained directly from humans. The use of stable tracers, being ethically justifiable, is a powerful tool for providing this information. As two tracers of the same element must be utilized in order to evaluate gut absorption, an analytical technique which is capable of distinguishing and measuring simultaneously different isotopes of zirconium in biological samples is required. Preliminary tests on laboratory animals were performed in order to assess the feasibility of the double tracer technique combined with proton activation analysis.

Dialdehyde sesquiterpenes and other terpenoids as vanilloids.

Selected naturally occurring unsaturated dialdehyde sesquiterpenes and related bioactive terpenoids were assayed for vanilloid-like activity. Out of the 25 compounds tested, eight inhibited completely the specific binding of [3H]resiniferatoxin by rat spinal cord membranes: binding affinities ranged from 0.6 microM for cinnamodial to 19.0 microM for hebelomic acid F. These values were comparable to the binding affinity of capsaicin (2.7 microM). With the exception of four ligands, compounds that inhibited resiniferatoxin binding to rat spinal cord membranes were also pungent on the human tongue where they showed cross-tachyphylaxis with capsaicin. As expected from their reactive nature, these compounds possess additional sites of action, as reflected in the complex behavior of the stimulation of calcium influx by cinnamodial and cinnamosmolide at high concentrations. This observation might explain the unexpectedly weak membrane depolarization by cinnamodial compared to capsaicin. We conclude that a range of sesquiterpene dialdehydes and related terpenoids, both pungent and non-pungent, may function as vanilloids. These compounds may represent a new chemical lead for the development of vanilloid drugs, structurally unrelated to either capsaicin or resiniferatoxin.

Five-Coordinate Hydrogen: Neutron Diffraction Analysis of the Hydrido Cluster Complex

Pentacoordinate hydrogen atoms were identified by single-crystal neutron diffraction analysis of [N(CH3)4]3[H2Rh13(CO)24]. The hydrogen atoms are located in square pyramidal cavities of the Rh13 cluster, in positions almost coplanar with the Rh4 faces on the surface of the cluster. They are slightly displaced inward, toward the central rhodium atom of the cluster, with average H-Rh(central) and H-Rh(surface) distances of 1.84(2) and 1.97(2) angstroms, respectively. This result shows that hydrogen, which normally forms only one bond, can be attached to five other atoms simultaneously in a large metal cluster.

The structures of new lanostane triterpenes from the fruiting bodies of Hebeloma senescens.

Three new lanostane triterpenes, hebelomic acids B[4], E[5], and F[6], were isolated from the inedible mushroom Hebeloma senescens. The latter two compounds are acyl derivatives of the new triterpene senescensol (12-deoxycrustulinol) [12]. The structures of compounds 4-6, including the absolute configuration of the 3-hydroxy-3-methylglutaric acid moiety, were established on the basis of spectral and chemical evidence.

New fatty acid esters of drimane sesquiterpenes from Lactarius uvidus.

This study of lipids of Lactarius uvidus has revealed the presence of new fatty acid esters of uvidin A [2a-d] and drimenol [6a-d]. Treatment of uvidin A [1] with base induced a Favorskii-like rearrangement leading to compounds with a new sesquiterpenoid skeleton. Uvidin A [1] showed insect antifeedant and cytotoxic activities.

Interaction of the pyrethroid insecticides tetramethrin and cypermethrin with enteric cholinergic transmission in the guinea-pig.

In electrically-stimulated longitudinal muscle-myenteric plexus preparations of the guinea-pig ileum, the Type I pyrethroid insecticide tetramethrin (1-100 microM) caused a biphasic response consisting of an early transient increase followed by a sustained decrease in the amplitude of cholinergic contractions. The cholinergic potentiation was antagonized by phenytoin (3 microM), which also prevented the increase in twitch height caused by veratridine (30 nM). The late inhibitory effect of tetramethrin probably involved a direct action on the musculature since contractile responses to applied acetylcholine (100 nM) or histamine (300 nM) were also depressed by this compound. Cypermethrin (1-100 microM), a Type II pyrethroid, had only a minor enhancing effect on electrically evoked contractions. Cypermethrin (30, 60 microM), but not tetramethrin, antagonized the cholinergic response induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (1-100 microM). These results suggest that neural Na+ channels activation may underlie pyrethroid-induced potentiation of enteric cholinergic transmission. In small intestine, however, cypermethrin is also effective as a noncompetitive antagonist of GABA-A receptor mediated cholinergic contractions.

A re-appraisal of the mode of action of 5-HT in inhibiting GABA-induced cholinergic contractions in the guinea-pig ileum.

In the guinea-pig ileum, pretreatment with 5-hydroxytryptamine (5-HT) (5 microM) for 4-5 min inhibited both 5-HT- and gamma-aminobutyric acid (GABA)-induced cholinergic contractions without consistently altering those induced by electrical field stimulation. Cisapride (1 micron) antagonized 5-HT-induced cholinergic contractions but left those induced by GABA or twitch responses unchanged. These results indicate that the 5-HT action in inhibiting GABA-induced cholinergic responses may arise at the interneuronal level, thus suggesting that GABA may also indirectly activate cholinergic terminal neurons. These findings rule out the possibility of 5-HT acting as an intermediate transmitter in this type of response.